Plasma cholesteryl ester transfer activity is modulated by the phase transition of the lipoprotein core

Abstract

Previous studies have shown that lipid transfer protein (LTP) activity is strongly temperature dependent, demonstrating a dramatic rise in activity near 37 degrees C. We have investigated the origin of this rapid rise in LTP activity. LTP-mediated transfers of radiolabeled cholesteryl ester (CE) from LDL to HDL, HDL to LDL, LDL to biotin-LDL, HDL to biotin-HDL, and between liposomes were determined as a function of assay temperature. Only assays containing LDL demonstrated this rapid rise in CE transfer activity. In contrast, TG transfer was almost linear with assay temperature. As human LDL CE undergoes a thermal phase transition near 37 degrees C, we investigated whether the rapid rise in CE transfer was dependent on this transition. Monkey LDL were isolated from animals consuming diets containing cholesterol and enriched in saturated, monounsaturated, or polyunsaturated fatty acids. With these LDL as substrate, the CE transfer between 21 degrees and 49 degrees C could be described by two straight lines, the intersection of which defined the inflection temperature. Among eight LDL samples, the inflection temperature was highly correlated with the CE phase transition determined by differential scanning calorimetry (r2 = 0.86). Both calorimetry and CE transfer activity inflection values were correlated with the saturated + monoene/polyene ratio of the LDL cholesteryl esters (r2 = 0.733 and 0.612, respectively). For LDL with inflection temperatures below 37 degrees C, CE transfer activity at 37 degrees C increased 10-14% for each 1 degree C decrease in the inflection temperature. We conclude that LTP activity is markedly affected by the physical state of the core CE. Diets rich in saturated fatty acids may result in LDL that are poor LTP substrates, which may hinder LTP's ability to promote normal lipoprotein remodeling.